Ab initio fragment molecular orbital calculations on the specific interactions between human, mouse and rat PPAR and GW409544

作者：Hayakawa Masato; Ohyama Tatsuya; Yamaguchi Yoko; Iwabuchi Shingo; Nakagawa Tomohiko; Nakajima Tamie; Kurita Noriyuki^*

来源：Molecular Simulation, 2010, 36(9): 644-656.

DOI：10.1080/08927021003671566

• peroxisome proliferator-activated receptor
• specific interactions
• electronic properties
• ab initio molecular orbital calculation
• molecular mechanics

To elucidate the specific interactions between the peroxisome proliferator-activated receptor (PPAR) and ligand GW409544 (GW), we obtained the solvated structures of the PPAR+GW complexes for human, mouse and rat by classical molecular mechanics calculations, and investigated their electronic properties by ab initio fragment molecular orbital calculations. The results indicate that the positively charged amino acids (Lys and Arg) of PPAR make a major contribution to the binding between PPAR and GW. In addition, it was clarified that Ser280 and Tyr314 of human and rat PPAR have a large attractive interaction with GW, while Ser280, Tyr314 and His440 of mouse PPAR have large interaction. These results on the difference in specific interactions between human and mouse/rat PPAR will be useful for predicting the effects of new chemicals on the human body based on the biomedical studies for the experimental animals such as mouse and rat.

• 出版日期2010